Effects of Collagen Heterogeneity on Myocardial Infarct Mechanics in a Multiscale Fiber Network Model.

ABSTRACT

The scar that forms after a myocardial infarction is often characterized by a highly disordered architecture but generally exhibits some degree of collagen fiber orientation, with a resulting mechanical anisotropy. When viewed in finer detail, however, the heterogeneity of the sample is clear, with different subregions exhibiting different fiber orientations. In this work, we used a multiscale finite element model to explore the consequences of the heterogeneity in terms of mechanical behavior. To do so, we used previously obtained fiber alignment maps of rat myocardial scar slices (n = 15) to generate scar-specific finite element meshes that were populated with fiber models based on the local alignment state. These models were then compared to isotropic models with the same sample shape and fiber density, and to homogeneous models with the same sample shape, fiber density, and average fiber alignment as the scar-specific models. All simulations involved equibiaxial extension of the sample with free motion in the third dimension. We found that heterogeneity led to a lower degree of mechanical anisotropy and a higher level of local stress concentration than the corresponding homogeneous model, and also that fibers failed in the heterogeneous model at much lower macroscopic strains than in the isotropic and homogeneous models. Taken together, these results suggest that scar heterogeneity may impair myocardial mechanical function both in terms of anisotropy and strength, and that individual variations in scar heterogeneity could be an important consideration for understanding scar remodeling and designing therapeutic interventions for patients after myocardial infarction.